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Advances in Histone Demethylase KDM3A as a Cancer Therapeutic Target

Lysine-specific histone demethylase 3 (KDM3) subfamily proteins are H3K9me2/me1 histone demethylases that promote gene expression. The KDM3 subfamily primarily consists of four proteins (KDM3A−D). All four proteins contain the catalytic Jumonji C domain (JmjC) at their C-termini, but whether KDM3C h...

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Autores principales: Yoo, Jung, Jeon, Yu Hyun, Cho, Ha Young, Lee, Sang Wu, Kim, Go Woon, Lee, Dong Hoon, Kwon, So Hee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280979/
https://www.ncbi.nlm.nih.gov/pubmed/32354028
http://dx.doi.org/10.3390/cancers12051098
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author Yoo, Jung
Jeon, Yu Hyun
Cho, Ha Young
Lee, Sang Wu
Kim, Go Woon
Lee, Dong Hoon
Kwon, So Hee
author_facet Yoo, Jung
Jeon, Yu Hyun
Cho, Ha Young
Lee, Sang Wu
Kim, Go Woon
Lee, Dong Hoon
Kwon, So Hee
author_sort Yoo, Jung
collection PubMed
description Lysine-specific histone demethylase 3 (KDM3) subfamily proteins are H3K9me2/me1 histone demethylases that promote gene expression. The KDM3 subfamily primarily consists of four proteins (KDM3A−D). All four proteins contain the catalytic Jumonji C domain (JmjC) at their C-termini, but whether KDM3C has demethylase activity is under debate. In addition, KDM3 proteins contain a zinc-finger domain for DNA binding and an LXXLL motif for interacting with nuclear receptors. Of the KDM3 proteins, KDM3A is especially deregulated or overexpressed in multiple cancers, making it a potential cancer therapeutic target. However, no KDM3A-selective inhibitors have been identified to date because of the lack of structural information. Uncovering the distinct physiological and pathological functions of KDM3A and their structure will give insight into the development of novel selective inhibitors. In this review, we focus on recent studies highlighting the oncogenic functions of KDM3A in cancer. We also discuss existing KDM3A-related inhibitors and review their potential as therapeutic agents for overcoming cancer.
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spelling pubmed-72809792020-06-15 Advances in Histone Demethylase KDM3A as a Cancer Therapeutic Target Yoo, Jung Jeon, Yu Hyun Cho, Ha Young Lee, Sang Wu Kim, Go Woon Lee, Dong Hoon Kwon, So Hee Cancers (Basel) Review Lysine-specific histone demethylase 3 (KDM3) subfamily proteins are H3K9me2/me1 histone demethylases that promote gene expression. The KDM3 subfamily primarily consists of four proteins (KDM3A−D). All four proteins contain the catalytic Jumonji C domain (JmjC) at their C-termini, but whether KDM3C has demethylase activity is under debate. In addition, KDM3 proteins contain a zinc-finger domain for DNA binding and an LXXLL motif for interacting with nuclear receptors. Of the KDM3 proteins, KDM3A is especially deregulated or overexpressed in multiple cancers, making it a potential cancer therapeutic target. However, no KDM3A-selective inhibitors have been identified to date because of the lack of structural information. Uncovering the distinct physiological and pathological functions of KDM3A and their structure will give insight into the development of novel selective inhibitors. In this review, we focus on recent studies highlighting the oncogenic functions of KDM3A in cancer. We also discuss existing KDM3A-related inhibitors and review their potential as therapeutic agents for overcoming cancer. MDPI 2020-04-28 /pmc/articles/PMC7280979/ /pubmed/32354028 http://dx.doi.org/10.3390/cancers12051098 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Yoo, Jung
Jeon, Yu Hyun
Cho, Ha Young
Lee, Sang Wu
Kim, Go Woon
Lee, Dong Hoon
Kwon, So Hee
Advances in Histone Demethylase KDM3A as a Cancer Therapeutic Target
title Advances in Histone Demethylase KDM3A as a Cancer Therapeutic Target
title_full Advances in Histone Demethylase KDM3A as a Cancer Therapeutic Target
title_fullStr Advances in Histone Demethylase KDM3A as a Cancer Therapeutic Target
title_full_unstemmed Advances in Histone Demethylase KDM3A as a Cancer Therapeutic Target
title_short Advances in Histone Demethylase KDM3A as a Cancer Therapeutic Target
title_sort advances in histone demethylase kdm3a as a cancer therapeutic target
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280979/
https://www.ncbi.nlm.nih.gov/pubmed/32354028
http://dx.doi.org/10.3390/cancers12051098
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